The main objective of this study is to look at the effect of iv acetate infusion on postprandial glucose metabolism and whether this effect differs between healthy lean subjects and obese subjects with metabolic syndrome.The secondary objectives of…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameters are the differences in postprandial glucose and
insulin levels upon a standardized mixed meal test (SMMT) consisting of
Nutridrink after acetate infusion.
Secondary outcome
The secundary study parameters are postprandial incretins (GLP-1 and ghreline),
insuline, glucose and lipid responses upon a SMM, subjective ratings of
appetite in fasted state, after exposure to virtual food stimuli and upon a SMM
and the CNS regulation of appetite upon virtual food stimuli and upon actual
food stimuli (measured by both VAS questionnaire and functional MRI).
Background summary
Obesity is a major public health problem. Mounting evidence suggest a prominent
role for the gut microbiome in pathophysiological pathways that influence the
central nervous system (CNS) regulation of food intake. In this regard, the
short-chain fatty acid (SCFA) acetate is one of the major metabolites produced
by gut microbiota from dietary fibre. It has been established that acetate is
absorbed into the blood stream and passes the blood brain barrier (BBB). In
rodent studies, acetate has been shown to function as a beneficial substrate in
hypothalamic brain regions to mediate both glucose metabolism and insulin
secretion as central appetite regulation. However, certain other studies have
shown contradicting results thus leaving the role of acetate in energy
metabolism and appetite regulation controversial. Moreover, the metabolic
effects of acetate in insulin resistant subjects appears to differ
significantly from the physiological situation. We therefore aim to study the
acute effects of intravenous (iv) infusion of the SCFA acetate on glucose
metabolism and neural regulation of food intake both in healthy lean subjects
and in obese subjects with metabolic syndrome.
Study objective
The main objective of this study is to look at the effect of iv acetate
infusion on postprandial glucose metabolism and whether this effect differs
between healthy lean subjects and obese subjects with metabolic syndrome.
The secondary objectives of this study are to study the effects of acetate
infusion on postprandial incretins (GLP-1 and ghreline), insuline, glucose and
lipid responses. Also both subjective ratings of appetite (VAS questionnaire)
as well as fMRI for CNS regulation of appetite will be determined.
Study design
Double blind, placebo controlled crossover design.
Intervention
All participants will receive either 1700 mL of sodium acetate with a
concentration of 150 mmol/L or sodium bicarbonate with a concentration of 150
mmol/L administered intravenously over a period of 180 minutes. Following a
crossover design, both interventions will be done in all participants in a
random order with a 1 week washout period in between.
Study burden and risks
The burden of this study is formed by the fasting from 20:30 the night before
testing until 13:00 on the day of the test except for the standardized mixed
meal (SMM). Also, a total of 320 ml blood will be drawn (which is lower than
the 500ml of blood taken at the bloodbank). Finally, an functional magnetic
resonance imaging (fMRI) scan of 1 hour will be made and this requires the
participants to lay still for 60 minutes, which could cause mild discomfort..
Furthermore, the intravenous administration of acetate can be considered low
risk since acetate is an endogenous molecule and the dosage that will be
administered for this study will not exceed physiological concentrations for a
long period of time. The fMRI scan will be preceded by a thorough screening
during which all possible exclusion criteria for undergoing an fMRI scan will
be ruled out and will therefore not be considered as a high risk procedure.
Meibergdreef 9
Amsterdam-Zuidoost 1105 AZ
NL
Meibergdreef 9
Amsterdam-Zuidoost 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
Inclusion criteria healthy lean subject group:
- Healthy Caucasian male or female
- Age 40-65
- Women must be post-menopausal
- BMI range of 19-25 kg/m²
- Subjects should be able and willing to give informed consent.
Inclusion criteria obese metabolic syndrome subject group:
- Caucasian male or female with metabolic syndrome
- Age 40-65
- Women must be post-menopausal
- BMI range of 25-40 kg/m²
- At least 3 out of 5 NCEP metabolic syndrome criteria: fasting plasma glucose
* 5.6 mmol/L and/or HOMA-IR * 2.5, triglycerides * 1.6 mmol/L,
waist-circumference > 102 cm, HDL cholesterol * 1.04 mmol/L, blood pressure *
130/85.
- Subjects should be able and willing to give informed consent.
Exclusion criteria
Exclusion criteria for all participants:
- Systemic medication use, except for paracetamol
- Oral or intravenous antibiotics in the past 3 months before inclusion
- Smoking
- Substance abuse
- Excessive weight loss (> 10% in past 3 monts)
- Overt diabetes mellitus type 2
- Malignancy (except for basal cell carcinoma)
- History of major heart disease
- History of major renal disease
- Pregnancy or breast feeding
- Implantable devices
- Contra-indication for MRI, such as claustrophobia or pacemaker
- Psychiatric illnesses: mood disorders, eating disorders, anxiety disorders,
schizophrenia and other psychotic disorders, dissociative disorders, somatoform
disorders, delirium, dementia and other cognitive disorders
- Simultaneous participation in other studies
- Inability to understand the study protocol, give informed consent or
participate adequately in study protocol
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL71072.018.19 |